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New targets for overactive bladder-ICI-RS 2109
Christopher Henry Fry1, Basu Chakrabarty1, Hikaru Hashitani2
1School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK.
Neurourology and Urodynamics
|November 19, 2019
Summary
Novel drug targets for overactive bladder (OAB) focus on bladder wall tissues and the storage phase of the micturition cycle. Research reviews pathways like cyclic nucleotides, beta-3 agonists, TRP channels, and antifibrosis agents for OAB management.
Area of Science:
- Pharmacology
- Urology
- Cell Biology
Background:
- Overactive bladder (OAB) significantly impacts quality of life.
- Current OAB treatments have limitations, necessitating novel therapeutic strategies.
- Identifying specific drug targets within the bladder wall is crucial for effective OAB management.
Purpose of the Study:
- To review existing evidence for novel drug targets for managing overactive bladder (OAB) symptoms.
- To propose new drug targets in the urinary bladder for OAB treatment based on literature and expert experience.
Main Methods:
- A think tank approach was employed, synthesizing literature evidence and research experience.
- Five key classes of agents or cellular pathways were evaluated for their potential in OAB treatment.
- Considered pathways include cyclic nucleotide signaling, novel beta-3 agonist targets, TRP channels, calcium-activated potassium channels, and antifibrosis agents targeting TGF-beta.
Main Results:
- Cyclic nucleotide pathways (cAMP, cGMP) influencing ATP release from nerves and urothelium were examined.
- Novel targets for beta-3 agonists, including bladder vasculature and muscularis mucosa, were identified.
- Several TRP channels (TRPV1, TRPV4, TRPA1, TRPM4) and small conductance Ca2+-activated K+ channels were implicated in detrusor overactivity and spontaneous contractions.
Conclusions:
- Specificity of drug action is a key consideration due to widespread distribution of target receptors/pathways.
- Further research is needed to detail OAB pathophysiology and direct drug specificity to bladder changes.
- Future targets should focus on the storage phase of the micturition cycle and encompass the entire bladder wall, not solely the detrusor muscle.
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